, Volume 446, Issue 4, pp 447-454
Date: 23 May 2003

Neuronal endoplasmic reticulum acts as a single functional Ca2+ store shared by ryanodine and inositol-1,4,5-trisphosphate receptors as revealed by intra-ER [Ca2+] recordings in single rat sensory neurones

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Abstract

We addressed the fundamentally important question of functional continuity of endoplasmic reticulum (ER) Ca2+ store in nerve cells. In cultured rat dorsal root ganglion neurones we measured dynamic changes in free Ca2+ concentration within the ER lumen ([Ca2+]L) in response to activation of inositol-1,4,5-trisphosphate receptors (InsP3Rs) and ryanodine receptors (RyRs). We found that both receptors co-exist in these neurones and their activation results in Ca2+ release from the ER as judged by a decrease in [Ca2+]L. Depletion of Ca2+ stores following an inhibition of sarco(endoplasmic)reticulum Ca2+-ATPase by thapsigargin or cyclopiazonic acid completely eliminated Ca2+ release via both InsP3Rs and RyRs. Similarly, when the store was depleted by continuous activation of InsP3Rs, activation of RyRs (by caffeine or 0.5 μM ryanodine) failed to produce Ca2+ release, and vice versa, when the stores were depleted by activators of RyRs, the InsP3-induced Ca2+ release disappeared. We conclude that in mammalian neurones InsP3Rs and RyRs share the common continuous Ca2+ pool associated with ER.